ECC1A_MYCTU
ID ECC1A_MYCTU Reviewed; 747 AA.
AC P9WNB3; L0TE12; O69735; Q7D4P6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=ESX-1 secretion system protein EccCa1 {ECO:0000305};
DE AltName: Full=ESX conserved component Ca1 {ECO:0000303|PubMed:19876390};
DE AltName: Full=Snm1 secretory protein {ECO:0000303|PubMed:14557536};
DE AltName: Full=Type VII secretion system protein EccCa1 {ECO:0000305};
DE Short=T7SS protein EccCa1 {ECO:0000305};
GN Name=eccCa1 {ECO:0000303|PubMed:19876390};
GN Synonyms=snm1 {ECO:0000303|PubMed:14557536}; OrderedLocusNames=Rv3870;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, SUBUNIT, INTERACTION WITH ECCCB1, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=14557536; DOI=10.1073/pnas.2235593100;
RA Stanley S.A., Raghavan S., Hwang W.W., Cox J.S.;
RT "Acute infection and macrophage subversion by Mycobacterium tuberculosis
RT require a specialized secretion system.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13001-13006(2003).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14756778; DOI=10.1046/j.1365-2958.2003.03844.x;
RA Guinn K.M., Hickey M.J., Mathur S.K., Zakel K.L., Grotzke J.E.,
RA Lewinsohn D.M., Smith S., Sherman D.R.;
RT "Individual RD1-region genes are required for export of ESAT-6/CFP-10 and
RT for virulence of Mycobacterium tuberculosis.";
RL Mol. Microbiol. 51:359-370(2004).
RN [4]
RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=16368961; DOI=10.1128/iai.74.1.88-98.2006;
RA Brodin P., Majlessi L., Marsollier L., de Jonge M.I., Bottai D.,
RA Demangel C., Hinds J., Neyrolles O., Butcher P.D., Leclerc C., Cole S.T.,
RA Brosch R.;
RT "Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on
RT immunogenicity and virulence.";
RL Infect. Immun. 74:88-98(2006).
RN [5]
RP NOMENCLATURE, AND SUBUNIT.
RX PubMed=19876390; DOI=10.1371/journal.ppat.1000507;
RA Bitter W., Houben E.N., Bottai D., Brodin P., Brown E.J., Cox J.S.,
RA Derbyshire K., Fortune S.M., Gao L.Y., Liu J., Gey van Pittius N.C.,
RA Pym A.S., Rubin E.J., Sherman D.R., Cole S.T., Brosch R.;
RT "Systematic genetic nomenclature for type VII secretion systems.";
RL PLoS Pathog. 5:E1000507-E1000507(2009).
RN [6]
RP SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19854905; DOI=10.1128/jb.01032-09;
RA Callahan B., Nguyen K., Collins A., Valdes K., Caplow M., Crossman D.K.,
RA Steyn A.J., Eisele L., Derbyshire K.M.;
RT "Conservation of structure and protein-protein interactions mediated by the
RT secreted mycobacterial proteins EsxA, EsxB, and EspA.";
RL J. Bacteriol. 192:326-335(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [8]
RP FUNCTION, POSSIBLE ACTIVITY REGULATION, AND MUTAGENESIS OF 35-PRO--GLY-92;
RP 276-HIS--THR-401; LYS-485; ARG-543 AND ARG-623.
RX PubMed=25865481; DOI=10.1016/j.cell.2015.03.040;
RA Rosenberg O.S., Dovala D., Li X., Connolly L., Bendebury A.,
RA Finer-Moore J., Holton J., Cheng Y., Stroud R.M., Cox J.S.;
RT "Substrates control multimerization and activation of the multi-domain
RT ATPase motor of type VII secretion.";
RL Cell 161:501-512(2015).
CC -!- FUNCTION: Part of the ESX-1 specialized secretion system, which
CC delivers several virulence factors to host cells during infection,
CC including the key virulence factors EsxA (ESAT-6) and EsxB (CFP-10).
CC {ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:16368961}.
CC -!- ACTIVITY REGULATION: EsxB binding to the second FtsK domain of EccCb1
CC causes multimerization; a subsequent unknown step relieves the
CC allosteric inhibition of linker 2 on FtsK domain 1 (this subunit),
CC activating the ATPase activity (PubMed:25865481).
CC {ECO:0000305|PubMed:25865481}.
CC -!- SUBUNIT: Part of the ESX-1 / type VII secretion system (T7SS), which is
CC composed of cytosolic and membrane components. The ESX-1 membrane
CC complex is composed of EccB1, EccCa1, EccCb1, EccD1 and EccE1
CC (PubMed:14557536, PubMed:16368961, PubMed:19876390). Interacts with
CC EccCb1 (PubMed:14557536). Residues 62-332 interact with EsxB and an
CC artificial EsxB-EsxA heterodimer (PubMed:19854905).
CC {ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:19854905, ECO:0000305|PubMed:19876390}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Disruption abolishes EsxA and EsxB secretion, but
CC not their expression (PubMed:14557536). It results in a lack of antigen
CC specific immunogenicity and leads to attenuated virulence
CC (PubMed:16368961). Mutants exhibit defects in bacterial growth during
CC the acute phase of a mouse infection (PubMed:14557536). No growth in
CC the human macrophage-like cell line THP-1, no cytotoxicity; bacteria
CC grow within cells but do not kill them and do not spread to other host
CC cells (PubMed:14756778). {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14756778, ECO:0000269|PubMed:16368961}.
CC -!- MISCELLANEOUS: In ESX-1 cluster, the FtsK/SpoIIIE-like protein is split
CC in two genes. {ECO:0000305}.
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DR EMBL; AL123456; CCP46699.1; -; Genomic_DNA.
DR PIR; D70802; D70802.
DR RefSeq; NP_218387.1; NC_000962.3.
DR RefSeq; WP_003899738.1; NZ_NVQJ01000074.1.
DR AlphaFoldDB; P9WNB3; -.
DR SMR; P9WNB3; -.
DR IntAct; P9WNB3; 1.
DR STRING; 83332.Rv3870; -.
DR PaxDb; P9WNB3; -.
DR DNASU; 886204; -.
DR GeneID; 45427874; -.
DR GeneID; 886204; -.
DR KEGG; mtu:Rv3870; -.
DR TubercuList; Rv3870; -.
DR eggNOG; COG1674; Bacteria.
DR OMA; GTHRQWS; -.
DR PhylomeDB; P9WNB3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0042783; P:evasion of host immune response; IMP:MTBBASE.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR023836; EccCa-like_Actinobacteria.
DR InterPro; IPR002543; FtsK_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01580; FtsK_SpoIIIE; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR03924; T7SS_EccC_a; 1.
DR PROSITE; PS50901; FTSK; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell inner membrane; Cell membrane; Membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..747
FT /note="ESX-1 secretion system protein EccCa1"
FT /id="PRO_0000393428"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 456..665
FT /note="FtsK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT ACT_SITE 600
FT /evidence="ECO:0000305|PubMed:25865481"
FT BINDING 479..486
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT MUTAGEN 33..92
FT /note="Missing: Cells unable to export EsxB, missing
FT transmembrane domain."
FT /evidence="ECO:0000269|PubMed:25865481"
FT MUTAGEN 276..401
FT /note="Missing: Cells unable to export EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
FT MUTAGEN 485
FT /note="K->T: Cells unable to export EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
FT MUTAGEN 543
FT /note="R->A: Decreased export of EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
FT MUTAGEN 623
FT /note="R->A: Cells unable to export EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
SQ SEQUENCE 747 AA; 80913 MW; CF6AA9153BE6F41E CRC64;
MTTKKFTPTI TRGPRLTPGE ISLTPPDDLG IDIPPSGVQK ILPYVMGGAM LGMIAIMVAG
GTRQLSPYML MMPLMMIVMM VGGLAGSTGG GGKKVPEINA DRKEYLRYLA GLRTRVTSSA
TSQVAFFSYH APHPEDLLSI VGTQRQWSRP ANADFYAATR IGIGDQPAVD RLLKPAVGGE
LAAASAAPQP FLEPVSHMWV VKFLRTHGLI HDCPKLLQLR TFPTIAIGGD LAGAAGLMTA
MICHLAVFHP PDLLQIRVLT EEPDDPDWSW LKWLPHVQHQ TETDAAGSTR LIFTRQEGLS
DLAARGPHAP DSLPGGPYVV VVDLTGGKAG FPPDGRAGVT VITLGNHRGS AYRIRVHEDG
TADDRLPNQS FRQVTSVTDR MSPQQASRIA RKLAGWSITG TILDKTSRVQ KKVATDWHQL
VGAQSVEEIT PSRWRMYTDT DRDRLKIPFG HELKTGNVMY LDIKEGAEFG AGPHGMLIGT
TGSGKSEFLR TLILSLVAMT HPDQVNLLLT DFKGGSTFLG MEKLPHTAAV VTNMAEEAEL
VSRMGEVLTG ELDRRQSILR QAGMKVGAAG ALSGVAEYEK YRERGADLPP LPTLFVVVDE
FAELLQSHPD FIGLFDRICR VGRSLRVHLL LATQSLQTGG VRIDKLEPNL TYRIALRTTS
SHESKAVIGT PEAQYITNKE SGVGFLRVGM EDPVKFSTFY ISGPYMPPAA GVETNGEAGG
PGQQTTRQAA RIHRFTAAPV LEEAPTP
